Iterative Experimental-Computational Design of Hydrogel Systems for Biomedical Applications

该奖项支持工程生物材料设计方法的基础研究。从历史上看，生物材料工程一直关注生物效应，但往往忽视了实现所需生物力学行为所需的先进材料制造和表征。本研究考虑了各向异性和层状水凝胶在组织工程中的应用。研究的结果将是设计这些生物材料的方法。它整合了制造和生物力学表征，目标是达到与人体复杂组织相对应的生物材料。考虑三个目标组织：气管，椎间盘和心脏瓣膜。研究成果将大大改善和加快工程进程，从而使工程生物材料更容易获得。研究成果还将通过学生直接参与研究、开发新的教育材料和指导本科高年级设计团队，整合到教育活动中。本项目的方法是一种迭代设计方法，用于具有区域依赖性质的各向异性和分层水凝胶系统。它集成了微结构水凝胶系统的制造工艺、实验和计算表征，以达到模拟结缔组织的生物材料。有纤维增强的组织（气管）、分层结构的组织（椎间盘）和既有图案又有层状的组织（心脏瓣膜）都被考虑在内。结合硅-体外设计过程依赖于软材料的制造、实验和计算力学以及数学之间的基本进展。迭代设计从图案或分层水凝胶样品的制备开始，这将遵循特定组织的拓扑结构。层和纤维模式的分子量的选择将使整体刚度接近真实组织在其最常见的状态（例如，椎间盘的压缩）。光刻和阶段交联将用于制造材料。样品将进行拉伸、压缩和弯曲测试。将通过本构公式整合实验数据，建立生物力学响应的计算模型。在简化的参数空间中进行粗级数值优化，以接近特定组织在所有可能的应力和变形状态下的目标行为。在初始结果的基础上，进一步制造和实验具有更复杂非均质性的水凝胶体系。模拟感兴趣组织的水凝胶系统将在全参数空间中应用该方法，从而实现最佳拓扑结构和组成。

This award supports fundamental research on methods for the design of engineered biomaterials. Historically, engineering of biomaterials has focused on biological effects but often ignored the advanced material fabrication and characterization needed to realize the desired biomechanical behavior. This research considers anisotropic and layered hydrogels for tissue engineering applications. The outcome of the research would be a methodology for the design these biomaterials. It integrates manufacturing and biomechanical characterization with the goal to arrive at biomaterials that correspond to complex tissues in the human body. Three target tissues are considered: trachea, intervertebral disks and heart valves. The research outcomes would greatly improve and accelerate the engineering process and thereby make engineered biomaterials more readily available. The outcomes of the research endeavor will also be integrated into educational initiatives through direct involvement of students in research, the development of new educational materials, and mentoring of undergraduate senior design teams.This project's approach is an iterative design methodology for anisotropic and layered hydrogel systems with regional dependent properties. It integrates manufacturing processes, experimental and computational characterization of the microstructured hydrogel systems to arrive at biomaterials that mimic connective tissues. Tissues with fibrous reinforcements (trachea), with layered structure (intervertebral disks), and tissue both patterned and layered (heart valves) are considered. The combined in silico-in vitro design process relies on fundamental advances at the interface between manufacturing, experimental and computational mechanics of soft materials, as well as mathematics. The iterative design starts with the preparation of samples of patterned or layered hydrogels, which will follow the topology of the specific tissue. Molecular weights for layers and for fiber patterns will be chosen such that the global stiffness approximates that of the real tissue in its most common state (e.g., compression for intervertebral disk). Photolithography and staged crosslinking will be used to manufacture materials. Samples will be tested in tension, compression, and bending. Computational models for the biomechanical response will be established which integrate the experimental data through constitutive formulations. Coarse level numerical optimization is performed in a reduced parameter space to approach the target behavior in all possible stress and deformation states encountered by the specific tissues. Further fabrication and experiments on hydrogel systems with more complex heterogeneity are then enabled based on the initial results. Hydrogel systems mimicking the tissue of interest would emerge from exercising the approach in the full parameter space such that optimal topologies and composition are achieved.